CLINICAL DILEMMA

A 30-year-old man with aplastic anemia (AA) presented with rapidly progressive exercise intolerance over a two-week period. His white blood cell count is 2.2×109/L with an absolute neutrophil count of 450/μL. Hemoglobin is 5.5 g/dL, and his platelet count is 3,000/μL. Lactate dehydrogenase is 180/μL and erythrocyte sedimentation rate is 89 mm/hr. Kidney and liver function is normal. A bone marrow (BM) biopsy shows scant lymphocytes and BM stromal cells. Hematopoietic elements are virtually absent. No signs of paroxysmal nocturnal hemoglobinuria by flow cytometry. The patient refuses packed red blood cells or platelet transfusions for religious reasons. We have started immunosuppressive treatment with anti-thymocyte globulin (ATG), steroids, and cyclosporine. Since the patient does not wish to receive transfusions, BM transplant is probably out of the question. Do you think it is reasonable to add erythropoietin, eltrombopag, or granulocyte colony-stimulating factor upfront? Is there anything else I am not thinking about?

EXPERT OPINION

Managing patients with bone marrow failure syndromes and religious objections to allogeneic blood product support is exceedingly challenging, especially in a younger individual with effective treatment options for the underlying disorder. I would divide management into immediate/near-term issues, and then the longer-term issues.

Focusing first on the immediate consequences of his bone marrow failure, ATG and cyclosporine are the mainstays of immunosuppressive treatment for individuals with AA who are not candidates for transplant. Responses, however, can take weeks to months. This individual’s most pressing concern is thrombocytopenia and his risk for bleeding. Antifibrinolytic agents such as tranexamic acid and aminocaproic acid have been studied for decades, reduce bleeding in individuals with thrombocytopenia, and appear safe in this population, but with mixed results concerning efficacy.1

Thrombopoietin-receptor agonists are effective in refractory AA, and have recently shown promise in the frontline setting.2 However, responses often take months. To help with anemia and granulocytopenia, erythropoietin agonists and filgrastim are unlikely to be effective, as his endogenous levels of these hormones are likely already high.3

The second issue is how to deal with longer-term prognosis in a young man with AA. Some individuals with religious objections to blood products accept stem cell transplants and are able to tolerate stem cell transplants without transfusions.4

To optimally care for this patient, my recommendations are:

Check his B12, folate, and iron and correct any deficiencies.

Check his erythropoietin level and supplement if inappropriately low.

Discuss with him the options for hematopoietic cell transplant.

Consider adding an antifibrinolytic agent while his platelet count is critically low.

Consider adding eltrombopag to his initial immunosuppression to maximize his chances of responding to therapy.

NEXT MONTH'S CLINICAL DILEMMA

A healthy 42-year-old woman not on estrogen flew 2.5 hours to North Carolina – plus time spent sitting in the terminal. She flew home two days later. The next morning she drove 2.5 hours to her sister’s home and returned home the following morning. Three days later she was diagnosed with a lower extremity deep vein thrombosis (DVT). Would you consider her DVT provoked or unprovoked? Would three months of anticoagulation be okay, or does she need D-dimers to help decide? If you consider her DVT to be unprovoked, how long should she be anticoagulated?

Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.

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